PROJECT SUMMARY AND ABSTRACT The University of Colorado Animal Imaging Shared Resource (AISR) is applying for funds to replace the existing 13-year old optical scanner IVIS200 and 12-year old Siemens Inveon microCT with a state-of-the-art multimodal system which bundles the 3D tomography IVIS Spectrum optical imager with the Quantum GX2 microCT scanner. The major users will be 23 investigators (with 28 active NIH R01 projects) from the University of Colorado Anschutz Medical Campus (CU Anschutz), with pending request for 3-10% of the Accessible User Time (AUT) per investigator. The requested system will become a part of the Colorado AISR (located within the CU Anschutz Vivarium), which is substantially supported as a major Institutional Technology Core by the University of Colorado Cancer Center (UCCC, P30 CA046934) and the Colorado Clinical and Translational Sciences Institute (CCTSI, UL1TR002535). The AISR was initially funded in 2005; presently, the animal imaging equipment includes Bruker 9.4 Tesla MRI scanner (2017 NIH S10 HEI), a Xenogen IVIS200, a Siemens Inveon microPET, a Siemens Inveon microCT, a Mediso microSPECT/CT, and an X-RAD high precision imaging guided irradiator. The AISR is the only comprehensive Animal Imaging Core in the State of Colorado and, since inception, has been utilized by 172 investigators (with over 75 being IVIS-users). The rationale for replacing the existing 13-year old IVIS200 (which has already reached its End-of-Life) with the combination of the IVIS Spectrum optical and Quantum GX2 microCT scanners lies in the expanded power of 3D anatomic and molecular imaging co-registration capacity, allowing for the accurate anatomical localization of the optical signal and depth corrected quantification of signal intensity. The IVIS Spectrum provides highly sensitive 3D molecular imaging of bioluminescence and fluorescence reporter genes and/or probes, all with transillumination and advanced spectral unmixing capabilities. The Quantum GX2 microCT, on the other hand, supports anatomical, physiological, functional and metabolic imaging via the large dynamic range, low dose, fast scanning, gating and high-resolution features. The system will be used for generating fused optical/ CT images, as well as a single high-throughput IVIS and a stand-alone in-vivo or specimen high-resolution microCT scanner. The AISR team has assembled a strong group of NIH funded principal investigators in the areas of oncology, neurooncology, regenerative medicine and nanotechnology who are the driving force for assembling this application. The estimated need for the major users in 2019 for optical imaging is 1,715 hours (90% of total AUT) and for microCT imaging is 1210 hours (76%). The AISR team is composed of a highly qualified translational imaging scientist, a veterinarian, an animal pathologist and five research assistants. The PI (Dr. Natalie Serkova) has a proven track record of 16 years for providing translational imaging services that are multi-modality, reliable and sustainable in a broad array of applications. A comprehensive financial and administrative infrastructure, generated by strong directorship and institutional support, is already in place to support the new systems and the Colorado AISR.